TY - JOUR
T1 - Interleukin-27 displays interferon-γ-like functions in human hepatoma cells and hepatocytes
AU - Bender, Herdis
AU - Wiesinger, Monique Y.
AU - Nordhoff, Carolin
AU - Schoenherr, Caroline
AU - Haan, Claude
AU - Ludwig, Stephan
AU - Weiskirchen, Ralf
AU - Kato, Nobuyuki
AU - Heinrich, Peter C.
AU - Haan, Serge
PY - 2009
Y1 - 2009
N2 - Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most studies, the effects of IL-27 on T cells were investigated; however, not much is known about possible effects of IL-27 on other cell types. IL-27 signals via the common IL-6 -type cytokine receptor chain gp130 and the IL-27 - specific chain WSX-1. Given the importance of gp130 in regulating liver responses such as the acute phase response or liver regeneration, we investigated whether IL-27 could also have a function in liver cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a sustained signal transducer and activator of transcription (STAT)1 and STAT3 activation. Whereas the STAT3 mediated responses to IL-27 (γ-fibrinogen and hepcidin induction) are not detectable, we observe an interferon-gamma (IFN-γ) - like STAT1 response leading to the induction of interferon-regulated proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9, myxovirus resistance A and guanylate binding protein 2. Conclusion: Our study provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and shows that IL-27 responses are not restricted to the classical immune cells. Our results suggest that IL-27 exerts IFN-like functions in liver cells and that it can contribute to the antiviral response in these cells.
AB - Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most studies, the effects of IL-27 on T cells were investigated; however, not much is known about possible effects of IL-27 on other cell types. IL-27 signals via the common IL-6 -type cytokine receptor chain gp130 and the IL-27 - specific chain WSX-1. Given the importance of gp130 in regulating liver responses such as the acute phase response or liver regeneration, we investigated whether IL-27 could also have a function in liver cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a sustained signal transducer and activator of transcription (STAT)1 and STAT3 activation. Whereas the STAT3 mediated responses to IL-27 (γ-fibrinogen and hepcidin induction) are not detectable, we observe an interferon-gamma (IFN-γ) - like STAT1 response leading to the induction of interferon-regulated proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9, myxovirus resistance A and guanylate binding protein 2. Conclusion: Our study provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and shows that IL-27 responses are not restricted to the classical immune cells. Our results suggest that IL-27 exerts IFN-like functions in liver cells and that it can contribute to the antiviral response in these cells.
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U2 - 10.1002/hep.22988
DO - 10.1002/hep.22988
M3 - Article
C2 - 19582813
AN - SCOPUS:68949187788
VL - 50
SP - 585
EP - 591
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 2
ER -